Characterization of prostanoid receptors mediating actions of the isoprostanes, 8-iso-PGE2 and 8-iso-PGF2α, in some isolated smooth muscle preparations

1 We investigated the contracting actions of the isoprostanes (isoPs), 8-iso-prostaglandin (PG) F-2 alpha and 8-iso-PGE(2), in comparison to the effects of the thromboxane (TX) A(2)-mimetic U 46619 and the traditional prostaglandin PGE(2) in the isolated rat aorta, isolated rat gastric fundus and the isolated guinea-pig ileum. 2 U 46619 and 8-iso-PGF(2 alpha) caused contractions in the rat aorta and rat gastric fundus in a concentration-dependent manner, whereas these agonists showed no effects in the guinea-pig ileum. However, 8-iso-PGE(2) and PGE(2) caused contractions in all isolated organs used. 3 The prostanoid TP-receptor antagonist SQ 29,548 (10 nM) Significantly antagonized vasoconstrictions induced by the agonists used in the rat aorta. SQ 29,548 at a final concentration of 3 mu M, but not at lower concentrations, significantly inhibited contractions induced by U 46619, 8-iso-PGF(2 alpha) and 8-iso-PGE(2) in the rat fundus. Responses to PGE(2) were unchanged. The prostanoid EP1-receptor antagonist SC 51089 (3 mu M) significantly inhibited contractions induced by 8-iso-PGE(2) and PGE(2) in the rat fundus and in the guinea-pig ileum. SC 51089 had no effect on responses to any of the agonists tested. 4 Our results show that 8-iso-PGE(2), in contrast to 8-iso-PGF(2 alpha), can also cause contractions by activation of the EP1-receptors in the rat gastric fundus and the guinea-pig ileum. The findings of the present study do not support the existence of a unique isoP-receptor in the tissues used.